Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults

Inger Hee Mathiesen, Mohammad Salem, Jan Gerstoft, Julie Christine Gaardbo, Niels Obel, Court Pedersen, Henrik Ullum, Susanne Dam Nielsen, Ann Brit Eg Hansen*

*Corresponding author for this work

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Abstract

Background: By assessing the changes in concentration of soluble receptor activator of nuclear factor Κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. Methods: We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation. Results: Soluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL. Conclusion: In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART. Trial registration:Clinical-Trial.gov. id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.

Original languageEnglish
Article number262
JournalBMC Infectious Diseases
Volume17
Number of pages7
ISSN1471-2334
DOIs
Publication statusPublished - 11. Apr 2017

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Computer Security
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Cytoplasmic and Nuclear Receptors
Immunoassay
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Keywords

  • BMD
  • CART
  • HIV infection
  • OPG
  • RANKL
  • RANK Ligand/metabolism
  • Humans
  • Middle Aged
  • Anti-HIV Agents/therapeutic use
  • Male
  • HIV Infections/drug therapy
  • Lymphocyte Count
  • Adult
  • Female
  • CD4-Positive T-Lymphocytes
  • Drug Therapy, Combination

Cite this

Mathiesen, Inger Hee ; Salem, Mohammad ; Gerstoft, Jan ; Gaardbo, Julie Christine ; Obel, Niels ; Pedersen, Court ; Ullum, Henrik ; Nielsen, Susanne Dam ; Hansen, Ann Brit Eg. / Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults. In: BMC Infectious Diseases. 2017 ; Vol. 17.
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title = "Changes in RANKL during the first two years after cART initiation in HIV-infected cART na{\"i}ve adults",
abstract = "Background: By assessing the changes in concentration of soluble receptor activator of nuclear factor Κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-na{\"i}ve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. Methods: We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation. Results: Soluble RANKL changed significantly over time (overall p = 0.02) with 25{\%} decrease (95{\%} CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL. Conclusion: In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART. Trial registration:Clinical-Trial.gov. id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.",
keywords = "BMD, CART, HIV infection, OPG, RANKL, RANK Ligand/metabolism, Humans, Middle Aged, Anti-HIV Agents/therapeutic use, Male, HIV Infections/drug therapy, Lymphocyte Count, Adult, Female, CD4-Positive T-Lymphocytes, Drug Therapy, Combination",
author = "Mathiesen, {Inger Hee} and Mohammad Salem and Jan Gerstoft and Gaardbo, {Julie Christine} and Niels Obel and Court Pedersen and Henrik Ullum and Nielsen, {Susanne Dam} and Hansen, {Ann Brit Eg}",
year = "2017",
month = "4",
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doi = "10.1186/s12879-017-2368-y",
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Mathiesen, IH, Salem, M, Gerstoft, J, Gaardbo, JC, Obel, N, Pedersen, C, Ullum, H, Nielsen, SD & Hansen, ABE 2017, 'Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults', BMC Infectious Diseases, vol. 17, 262. https://doi.org/10.1186/s12879-017-2368-y

Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults. / Mathiesen, Inger Hee; Salem, Mohammad; Gerstoft, Jan; Gaardbo, Julie Christine; Obel, Niels; Pedersen, Court; Ullum, Henrik; Nielsen, Susanne Dam; Hansen, Ann Brit Eg.

In: BMC Infectious Diseases, Vol. 17, 262, 11.04.2017.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults

AU - Mathiesen, Inger Hee

AU - Salem, Mohammad

AU - Gerstoft, Jan

AU - Gaardbo, Julie Christine

AU - Obel, Niels

AU - Pedersen, Court

AU - Ullum, Henrik

AU - Nielsen, Susanne Dam

AU - Hansen, Ann Brit Eg

PY - 2017/4/11

Y1 - 2017/4/11

N2 - Background: By assessing the changes in concentration of soluble receptor activator of nuclear factor Κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. Methods: We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation. Results: Soluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL. Conclusion: In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART. Trial registration:Clinical-Trial.gov. id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.

AB - Background: By assessing the changes in concentration of soluble receptor activator of nuclear factor Κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. Methods: We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation. Results: Soluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL. Conclusion: In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART. Trial registration:Clinical-Trial.gov. id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.

KW - BMD

KW - CART

KW - HIV infection

KW - OPG

KW - RANKL

KW - RANK Ligand/metabolism

KW - Humans

KW - Middle Aged

KW - Anti-HIV Agents/therapeutic use

KW - Male

KW - HIV Infections/drug therapy

KW - Lymphocyte Count

KW - Adult

KW - Female

KW - CD4-Positive T-Lymphocytes

KW - Drug Therapy, Combination

U2 - 10.1186/s12879-017-2368-y

DO - 10.1186/s12879-017-2368-y

M3 - Journal article

C2 - 28399815

VL - 17

JO - B M C Infectious Diseases

JF - B M C Infectious Diseases

SN - 1471-2334

M1 - 262

ER -